Synthetic organic catalysts for carrying out organic reactions will be designed, synthesized, and studied. The investigation is inspired by the catalytic properties of enzymes. In some cases the arrangement and character of the catalyzing functional groups are guided by those enzymes whose structures and functions are known. The binding sites and support structures in our host catalysts will be nonpeptide multi-heteromacrocycles. Their molecular weights are kept below 3000. Desirable properties sought in our catalysts are structural simplicity, synthetic viability, chemical stability, rapid rates, high chemical yields, high turnover, high regiospecficity, and high stereospecficity. These catalysts are hosts whose support structures possess enforced concave surfaces of molecular dimensions on which are placed convergently arranged polar binding and catalytic sites. These host sites act cooperatively to collect and orient guest reactants with complementary and divergently arranged binding sites. The reaction rates of the guests are accelerated by lowering the activation energies of reactions by complexation and stabilization of their transition states. Some host catalysts are designed to operate in water, and others in organic media. Synthetic transacylases, aldolases, hydrolases, polymerases, and cycloaddition catalysts will be designed, synthesized, and tested. The catalyst systems are designed with the help of Corey-Pauling-Koltun molecular models. The structures of host-guest reactant models are determined by X-ray and NMR spectroscopy. Target catalysts are selected on the basis of their potential importance, the viability of their synthesis, and the yield of knowledge expected from their investigation. Specific aims for the next year of support involve studies of: 1) a transacylase modeled on chymotrypsin; 2) a phosphate ester hydrolase modeled after ribonuclease; 3) application of affinity labeling reactions to highly structured host-guest complexes as a synthetic tool for remote functionalization of hosts; 4) development of systems with enforced concave surfaces of molecular dimensions as synthetic vessels for carrying out organic reactions; 5) development of chiral catalysts for turning prochiral starting materials into single enantiomers. Studies 1), 2), and 5) are under way. Studies 3) and 4) are now commencing.